This invention relates to topical compositions for application to human skin and to their use in improving the condition and appearance of skin.
Skin is subject to deterioration through dermatological disorders, environmental abuse (wind, air conditioning, central heating) or through the normal ageing process (chronoageing) which may be accelerated by exposure of skin to sun (photoageing). In recent years the demand for cosmetic methods for improving the appearance and condition and, in particular, for reversing, reducing or preventing the visible signs of wrinkled, aged and/or photodamaged skin has grown enormously.
Consumers are increasingly seeking xe2x80x9canti-ageingxe2x80x9d cosmetic products that reverse, treat or delay the visible signs of chronoaging and photoaging skin such as wrinkles, lines, sagging, hyperpigmentation and age spots.
Collagen, the predominant matrix skin protein is known to impart tensile strength to skin. It is also known in the art that the levels of collagen in skin are significantly reduced with aged and/or photodamaged skin. Many studies have shown that the levels of collagen type I in skin is decreased with age and/or with increased photodamage, (for example Lavker, R. J.Inv.Derm., (1979), 73, 79-66; Griffiths et al. N. Eng. J. med.(1993) 329, 530-535. The reduction of the levels of collagen in skin is accordingly associated with a decrease in the tensile strength of the skin causing wrinkles and laxity.
It is well known in the art that retinoic acid is a potent anti-ageing active and induces dermal repair of photodamaged skin. It has been shown that wrinkle effacement and dermal repair following topical treatment of skin with retinoic acid arises through new collagen deposition and synthesis in the skin (for example, Griffiths et al. N. Eng. J. med. (1993) 329, 530-535). It is widely accepted that strengthening of the dermal matrix by boosting the level of collagen in skin using retinoic acid provides anti-ageing/dermal repair benefits.
J05271046 describes a skin composition that contains an unsaturated fatty acid having 18 to 22 carbons and two or more unsaturated bonds, such as linoleic and arachidonic acid and a polyphenol. This composition is useful for lightening the skin.
Use of oils rich in petroselinic acid in skin care compositions as a moisturising agent has been described in EP A 0709084.
The use of fatty acids, including petroselinic acid, in cosmetic formulations for treating the hair is known. EP-A-116439 describes hair tonics, which include fatty acids, such as petroselinic acid, linoleic acid, linolenic acid oleic acid and arachidonic acid for alleviating dandruff and for stimulating hair growth.
We have now found that effective treatment and prevention of normal, but cosmetically undesirable, skin conditions, due to chronoaging or photoaging, such as wrinkles, lines, sagging, hyperpigmentation and age spots, may be obtained through the application of cosmetic compositions to the skin which comprises a specific combination of two lipid components.
The art discussed above does not disclose the specific synergistic combination of a first lipid component selected from petroselinic acid or docosahexaenoic acid together with a second lipid component, nor the use of such a specific combination for treating ageing skin.
According to a first aspect of the present invention there is provided a topical composition comprising:
(a) a first lipid component selected from petroselinic acid and/or docosahexaenoic acid and/or derivatives thereof;
(b) a second lipid component which is an activator of peroxisome proliferator activated receptors of sub-type alpha and/or derivatives thereof and/or mixtures thereof; and
(c) a dermatologically acceptable vehicle.
According to a second aspect of the present invention there is provided a cosmetic method of providing at least one skin care benefit selected from: treating/preventing wrinkling, sagging, dry, aged and/or photodamaged skin; boosting collagen deposition in skin, boosting decorin production in skin, enhancing tissue repair; improving skin texture, smoothness and/or firmness; the method comprising applying to the skin a topical composition as described above.
The present invention also encompasses the use of the inventive compositions for providing at least one skin care benefit selected from treating/preventing wrinkling, sagging, aged and/or photodamaged skin; boosting collagen deposition in skin, boosting decorin production in skin, enhancing tissue repair; and improving skin texture, smoothness and/or firmness.
According to a still further aspect of the present invention there is provided the use of a first lipid component selected from petroselinic acid and/or docosahexaenoic acid and/or derivatives thereof in combination with a second lipid component which is an activator of the peroxisome proleferator activated receptor sub-type alpha and/or derivatives thereof and/or mixtures thereof in a cosmetic topical composition for providing at least one cosmetic skin care benefit selected from treating/preventing wrinkling, sagging, aged and/or photodamaged skin; boosting collagen deposition in skin, boosting decorin production in skin, enhancing tissue repair; and improving skin texture, smoothness and/or firmness.
The inventive compositions, methods and uses thus provide anti-ageing benefits which result in the promotion of smooth and supple skin with improved elasticity and a reduced or delayed appearance of wrinkles and aged skin, with improved skin colour. A general improvement in the appearance, texture and condition, in particular with respect to the radiance, clarity, and general youthful appearance of skin is achieved.
The term xe2x80x9ctreatingxe2x80x9d as used herein includes within its scope reducing, delaying and/or preventing the above mentioned normal, but cosmetically undesirable, skin conditions caused by the normal ageing process. The visible signs of aging, such as wrinkles, lines and/or sagging are delayed or reduced. Generally, the quality of skin is enhanced and its appearance and texture is improved by preventing or reducing wrinkling and increasing flexibility, firmness, smoothness, suppleness and elasticity of the skin. The compositions, methods and uses according to the invention may be useful for treating skin that is already in a wrinkled, aged, and/or photodamaged condition or for treating youthful skin to prevent or reduce those aforementioned undesirable changes due to the normal ageing/photoageing process.
Petroselinic Acid and Docosahexaenoic Acid
Petroselinic acid (hereinafter referred to as PA) is a monounsaturated long chain (C18) fatty acid, having the formula CH3(CH2)10CHxe2x95x90CH(CH2)4COOH.
Docosahexaenoic acid (hereinafter referred to as DHA) is a polyunsaturated long chain (C22) fatty acid having the formula CH3(CH2CHxe2x95x90CH)6CH2CH2COOH.
The invention also includes derivatives of the free acid which thus comprise petroselinic acid/docosahexaenoic acid moieties. Preferable derivatives include those derived from substitution of the carboxyl group of the acid, such as esters (e.g. triglyceride esters, monoglyceride esters, diglyceride esters, phosphoesters), amides (e.g. ceramide derivatives), salts (e.g. alkali metal and alkali earth metal salts, ammonium salts); and/or those derived from substitution of the C18/C22 carbon chain, such as alpha hydroxy and/or beta hydroxy derivatives.
In the case of triglyceride ester derivatives, all positional isomers of PA/DHA substituents on the glycerol backbone are included. The triglycerides must contain at least one PA/DHA moiety. For example, of the three esterifiable positions on the glycerol backbone, the 1 and 2 positions may be esterified with PA/DHA and by another lipid at position 3 or as an alternative, the glycerol backbone could be esterified by PA/DHA at the 1 and 3 positions with another lipid at position 2.
Oils that are rich in petroselinic acid triglyceride are thus also suitable for use in the present invention. Such oils are commercially available and include parsley seed oil, carrot seed oil, fennel fruit oil, parsnip seed oil, coriander seed oil, chervil seed oil, caraway plant oil, and celery seed oil.
Oils that are rich in the DHA triglyceride are also suitable for use in the present invention. Such oils are commercially available and include fish oils and their concentrates.
Wherever the term xe2x80x9cpetroselinic acidxe2x80x9d or xe2x80x9cPAxe2x80x9d or xe2x80x9cdocosahexaenoic acidxe2x80x9d or xe2x80x9cDHAxe2x80x9d is used in this specification it is to be understood that the derivatives thereof comprising PA/DHA moieties are also included. xe2x80x9cPA/DHA moietiesxe2x80x9d refers to PA/DHA fatty acyl portion(s) of a PA/DHA derivative.
The PA and or DHA to be employed in accordance with the present invention is present in the topical composition in an effective amount. Normally the total amount of the active is present in an amount between 0.0001% and 50% by weight of the composition. More preferably the amount is from 0.01% to 10% and most preferably from 0.1% to 5% in order to maximise benefits at a minimum cost. Where the first lipid is DHA or a DHA derivative, preferably it is present at a level of less than 3% by weight to avoid any potential odour problems.
Lipid Activators of Peroxisome Proliferator Activated Receptors of Sub-Type xcex1
The term xe2x80x9cactivator of peroxisome proliferator activated receptors of sub-type xcex1xe2x80x9d or xe2x80x9cPPAR xcex1 activatorxe2x80x9d in the present application means a lipid that activates the nuclear receptor PPAR xcex1.
Peroxisome proliferator activated receptors are a known family of nuclear hormone receptors having three subtypes, xcex1, xcex2, xcex3, of varying tissue distribution. Peroxisome proliferator activated receptors subtype xcex1 (hereinafter referred to as PPAR xcex1) are present in skin. Lipid activators of PPAR xcex1 such as linoleic acid are well known in the art. These have been shown to accelerate skin epidermal barrier development in vitro (Hanley et al,(1997) J.Clin.Inv 100,705-712). However, there is no disclosure or suggestion in the art of activators of PPAR xcex1 having use in cosmetic compositions for providing cosmetic anti-ageing treatments.
An established and widely accepted method by which PPAR activation can be demonstrated and thus by which lipid activators of PPARs can be identified is the reporter gene assay. Lipids that are activators of PPAR xcex1 are thus easily identifiable by those skilled in the art as those compounds which cause expression of luciferase or chloramphenicol acetyl transferase (hereinafter referred to as CAT) in the reporter gene assay outlined in Example 1 belowxe2x80x94the full protocol is provided by Kliewer et al. (1992) Nature, 358, 771-774.
Thus if a lipid compound passes this in vitro reporter gene assay, that is it causes expression of luciferase or CAT in the reporter gene assay outlined in Example 1 below, it is included as a lipid PPAR xcex1 activator even if it is not specifically mentioned herein. In a preferred embodiment of the invention, the lipid PPAR xcex1 activator is a compound which promotes activation of the reporter gene at least 2-fold above background levels as these are the more effective anti-ageing agents.
Examples of lipid PPAR xcex1 activators which satisfy the reporter gene assay test include C10-C18 saturated fatty acids which preferably are branched, or preferably derivatised (eg with hydroxy groups) if straight chain, C10-C20 monounsaturated fatty acids and C10-C22 polyunsaturated fatty acids.
The fatty acids may be straight or branched chain, saturated or unsaturated and may be substituted e.g. hydroxylated such as alpha hydroxy or beta hydroxy derivatives. The corresponding alcohols, triglycerides and phospholipids of any of those acids are also suitable for use in the present invention. Preferable derivatives include those derived from substitution of the carboxyl group of the acid, such as esters (e.g. triglyceride esters, monoglyceride esters, diglyceride esters, phosphoesters), amides (e.g. ceramide derivatives), salts (e.g. alkali metal and alkali earth metal salts, ammonium salts). In the case of triglyceride ester derivatives, all positional isomers on the glycerol backbone are included.
Oils that are rich in fatty acid triglyceride are thus also suitable for use in the present invention. Such oils are commercially available and include coriander seed (rich in petroselinic acid), parsley seed oil (rich in petroselinic acid), evening primrose oil, (rich in gamma linolenic acid), borage seed oil (rich in gamma linolenic acid), Shea butter (rich in oleic and linoleic acid), fish oils and their concentrates (rich in DHA and EPA), cramb oil (rich in erucic acid) linseed oil (rich in alpha linolenic acid), almond oil (rich in oleic acid) and cotton seed oil (rich in linoleic acid).
Preferable PPAR xcex1 activators according to the invention are 12-hydroxystearic acid, cis parinaric acid, trans-7-octadecenoic acid, cis 5,8,11,14,17 eicosapentanoic acid, cis-4,7,10,13,16,19 docosahexenoic acid, cojugated linoleic acid (c9,t11), columbinic acid, linolenelaidic acid, ricinolaidic acid, stearidonic acid, 2-hydroxystearic acid, alpha-linolenic acid, arachidonic acid, cis-11,14-eicosadienoic acid, conjugated linoleic (t10,c12), conjugated linoleic acid (t9,t11), conjugated linoleic acid (50:50 mix of c9, t11 and t10 c12), coriander acids, linolelaidic acid, monopetroselinic acid, petroselinic acid, ricinoleic acid, stearolic acid, thuja extract and trans vaccenic acid.
Further suitable preferred PPAR xcex1 activators include cis-11,14,17 eicosatrienoic acid, cis-5 eicosenoic acid, cis-8,11,14 eicosatrienoic acid, hexadecatrienoic acid, palmitoleic acid, petroselaidic acid, trans trans farnesol, cis 13, 16 docosadienoic acid, cis vaccenic acid, cis-11 eicosenoic acid, cis-13,16,19 docosatrienoic acid, cis-13-octadecenoic acid, cis-15-octadecanoic acid, cis-7,10,13,16 docosatetraenoic acid, elaidic acid, gamma-linolenic acid, geranic acid, geranyl geranoic acid, linoleic acid, oleic acid, petroselinyl alcohol, phytanic acid, pinolenic acid, trans-13-octadecenoic acid, tridecyl salicylic acid (TDS).
A further suitable category of PPAR xcex1 activators include plant extracts, such as biochanin A (red clover phytoestrogen), chromolaena odorata extract, pomegranate saponifiable hydrolysable extract, buglossoides (stearidonic plant extract), and zanthalene (extract from Sichuan peppercorn).
Particularly preferred lipids, due to their superior anti-ageing effects when combined with petroselinic acid and or DHA (or derivatives thereof) in accordance with the present invention, are selected from the group comprising polyunsaturated fatty acids such linoleic acid, conjugated linoleic acid, linolenic acid eicosatetraynoic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic (DHA) acid (for DHA, only where the first lipid of the inventive composition is PA or derivatives thereof), monounsaturated fatty acids such as petroselinic acid (for PA only where the first lipid of the inventive composition is DHA or derivatives thereof), elaidic acid, oleic acid, erucic acid, and dioic acids such hexadecanedioc acid.
It should also be understood that the PPAR xcex1 activator which is present in compositions according to the invention is ideally present in the xe2x80x9cactivexe2x80x9d form; that is, it is not esterified. As such, whilst natural sources of the material such as oils are referred to above, the PPAR xcex1 activator which is used in compositions according to the invention is preferably not the raw, esterified form of the activator, but rather a raw material source which is either rich in the unesterified PPAR xcex1 activator, or one in which the esterified form has been hydrolysed to release the fatty acid.
The second lipid component is employed in the inventive composition in an amount of between 0.0001% and 50% by weight of the composition. More preferably the amount is from 0.01% to 10% and most preferably from 0.1% to 5% in order to maximise benefits at a minimum cost.
Dermatologically Acceptable Vehicle
The composition used according to the invention also comprises a dermatologically/cosmetically acceptable vehicle to act as a dilutant, dispersant or carrier for the actives. The vehicle may comprise materials commonly employed in skin care products such as water, liquid or solid emollients, silicone oils, emulsifiers, solvents, humectants, thickeners, powders, propellants and the like.
The vehicle will usually form from 5% to 99.9%, preferably from 25% to 80% by weight of the composition, and can, in the absence of other cosmetic adjuncts, form the balance of the composition.
Optional Skin Benefit Materials and Cosmetic Adjuncts
Besides the actives, other specific skin-benefit actives such as sunscreens, skin-lightening agents, skin tanning agents may also be included. The vehicle may also further include adjuncts such as antioxidants, perfumes, opacifiers, preservatives, colourants and buffers.
Product Preparation, Form, Use and Packaging
To prepare the topical composition used in the method of the present invention, the usual manner for preparing skin care products may be employed. The active components are generally incorporated in a dermatologically/cosmetically acceptable carrier in conventional manner. The active components can suitably first be dissolved or dispersed in a portion of the water or another solvent or liquid to be incorporated in the composition. The preferred compositions are oil-in-water or water-in-oil or water-in-oil-in-water emulsions.
The composition may be in the form of conventional skin-care products such as a cream, gel or lotion, capsules or the like. The composition can also be in the form of a so-called xe2x80x9cwash-offxe2x80x9d product, e.g. a bath or shower gel, possibly containing a delivery system for the actives to promote adherence to the skin during rinsing. Most preferably the product is a xe2x80x9cleave-onxe2x80x9d product; that is, a product to be applied to the skin without a deliberate rinsing step soon after its application to the skin.
The composition may packaged in any suitable manner such as in a jar, a bottle, tube, roll-ball, or the like, in the conventional manner. It is also envisaged that the inventive compositions could be packaged as a kit of two separate compositions, one containing the first lipid component petroselinic acid and/or DHA the second containing the second lipid component of the present invention, to be applied to the skin simultaneously or consecutively.
The composition according to the invention may also be formulated into a form suitable for oral ingestion such as a capsule, tablet or similar.
The method of the present invention may be carried out one or more times daily to the skin which requires treatment. The improvement in skin appearance will usually become visible after 3 to 6 months, depending on skin condition, the concentration of the active components used in the inventive method, the amount of composition used and the frequency with which it is applied. In general, a small quantity of the composition, for example from 0.1 to 5 ml is applied to the skin from a suitable container or applicator and spread over and/or rubbed into the skin using the hands or fingers or a suitable device. A rinsing step may optionally follow depending on whether the composition is formulated as a xe2x80x9cleave-onxe2x80x9d or a xe2x80x9crinse-offxe2x80x9d product.